Although cell-mediated immune responses to a variety of alloantigenic stimuli have been studied thoroughly in the past, responses that occur after prior alloantigenic stimulation have not been previously thoroughly investigated. Our studies involve an assessment of cell-mediated immune responses after the host has responded to a variety of alloantigenic stimulation to the same and other antigens. We find a marked specific decrease in the generation of cytotoxic cells after previous immunizations. The diminished response is largely specific for the immunizing alloantigen. Mechanisms involved in this suppression include elimination of graft proliferation in immunized hosts, elimination of stimulator cells by cytotoxic cells, and depression by alloantisera. The significance of this work comes from attempts to understand regulatory mechanisms of cellular immune responses.